Synthetic multiple tandem repeat mucin and mucin-like peptides, and uses thereof

Abstract

The present invention relates to novel synthetic muc-1 peptides and muc-1 analogs comprising at least two 20-amino acid tandem repeats of muc-1, wherein said synthetic muc-1 peptide is capable of attaining native conformation in the absence of glycosylation. The invention also relates methods of producing the peptides. The invention further relates to uses of the peptides, such as for vaccines and diagnostic testing.

What is claimed is: 
     
       1. A synthetic muc-1 peptide 105 amino acids in length comprising five sequential 20-amino acid tandem repeats of muc-1 and five additional amino acids, which five additional amino acids either precede the first of the five sequential 20-amino acid tandem repeats or follow the fifth of the five sequential 20-amino acid tandem repeats, wherein said synthetic muc-1 peptide attains native conformation in the absence of glycosylation. 
     
     
       2. A composition comprising at least one synthetic muc-1 peptide according to claim 1 covalently linked to a pharmaceutically acceptable carrier molecule. 
     
     
       3. An immunogenic composition capable of inducing a mammal to produce antibodies specific for an amino acid sequence corresponding to an epitope present on a cancer cell that does not express muc-1, wherein said immunogenic composition comprises a synthetic peptide comprising at least two 20-amino acid tandem repeats of muc-1 and at least one foreign amino acid sequence corresponding to an epitope present on a cancer cell that does not express muc-1, which foreign amino acid sequence is inserted as a substitution within an amino acid sequence PDTRP in the at least two 20-amino acid tandem repeats of muc-1, wherein said synthetic peptide attains native conformation in the absence of glycosylation and when the foreign amino acid sequence is present in the synthetic peptide. 
     
     
       4. The immunogenic composition according to claim 3, wherein said synthetic peptide is 105 amino acids in length and comprises five sequential 20-amino acid tandem repeats of muc-1 and five additional amino acids, which five additional amino acids either precede the first of the five sequential 20-amino acid tandem repeats or follow the fifth of the five sequential 20-amino acid tandem repeats, and at least one foreign amino acid sequence corresponding to an epitope present on a cancer cell that does not express muc-1, which foreign amino acid sequence is inserted as a substitution within an amino acid sequence PDTRP in the at least five sequential 20-amino acid tandem repeats of muc-1. 
     
     
       5. A method of producing immunity to cancer that does not express muc-1, comprising the step of administering the immunogenic composition according to claim 3 to a mammal in an immunogenically effective amount. 
     
     
       6. A cancer vaccine comprising a synthetic peptide comprising at least two 20-amino acid tandem repeats of muc-1 and at least one foreign amino acid sequence corresponding to an epitope present on a cancer cell that does not express muc-1, which foreign amino acid sequence is inserted as a substitution within an amino acid sequence PDTRP in the at least two 20-amino acid tandem repeats of muc1, wherein said synthetic peptide attains native conformation in the absence of glycosylation and when the foreign amino acid sequence is present in the synthetic peptide. 
     
     
       7. The cancer vaccine according to claim 6, wherein said synthetic peptide is 105 amino acids in length comprising five sequential 20-amino acid tandem repeats of muc-1 and five additional amino acids, which five additional amino acids either precede the first of the five sequential 20-amino acid tandem repeats or follow the fifth of the five sequential 20-amino acid tandem repeats, and at least one foreign amino acid sequence corresponding to an epitope present on a cancer cell that does not express muc-1, which foreign amino acid sequence is inserted as a substitution within an amino acid sequence PDTRP in the five sequential 20-amino acid tandem repeats of muc-1. 
     
     
       8. A method of producing immunity to a cancer that does not express muc-1, comprising the step of administering the vaccine according to claim 6 to a mammal in an immunogenically effective amount. 
     
     
       9. An immunogenic composition capable of inducing in a mammal antibodies against a cancer epitope of a cancer that expresses muc-1 which comprises a synthetic peptide 105 amino acids in length comprising five 20-amino acid tandem repeats of muc-1 and five additional amino acids, which five additional amino acids either precede the first of the five sequential 20-amino acid tandem repeats or follow the fifth of the five sequential 20-amino acid tandem repeats, wherein said synthetic muc-1 peptide attains native conformation in the absence of glycosylation. 
     
     
       10. A method of producing immunity to cancer that expresses muc-1, comprising the step of administering the immunogenic composition according to claim 9 to a mammal in an immunogenically effective amount. 
     
     
       11. A cancer vaccine for a cancer that expresses muc-1, comprising a synthetic muc-1 peptide 105 amino acids in length, which comprises five 20-amino acid tandem repeats of muc-1 and 5 additional amino acids, which five additional amino acids either precede the first of the five sequential 20-amino acid tandem repeats or follow the fifth of the five sequential 20-amino acid tandem repeats, and said synthetic muc-1 peptide attains native conformation in the absence of glycosylation.